Most Accessed Articles – Recent Advances and Future Perspectives in Pharmaceutical Analysis

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Journal Name: Current Pharmaceutical Analysis

Author(s): Nurgul K. Bakirhan, Sibel A. Ozkan*.

Abstract:

The role of the analytical methods and their validations has been important in quantification of drugs from their dosage forms or biological samples in recent years. Development of analytical methodscoupled with each other, is useful for the investigation of behavior of drugs or metabolites or impurities, and is also a useful tool for sensitive detections. The recent roles of spectroscopy, chromatography, titrimetry, electrochemistry and capillary electrophoresis have been explained here. To read out more, please visit: http://www.eurekaselect.com/176047/article

Most Accessed Articles | Assessment of Auditory Pathways Using Diffusion Tensor Imaging in Patients with Neurofibromatosis Type 1

Journal Name: Current Medical Imaging
Formerly: Current Medical Imaging Reviews

 

 

Graphical Abstract:

Abstract:

Aim: The aim of our study was to determine whether the diffusion properties of the auditory pathways alter between patients with Neurofibromatosis type 1 (NF1) and the healthy subjects. DTI can well demonstrate FA and ADC changes in auditory tracts and it may be a guide to identify the candidates for hearing loss among NF1 children.

Methods: The study population consisted of 43 patients with NF1 and 21 healthy controls. Diffusion tensor imaging (DTI) was used to measure apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values from lemniscus lateralis, colliculus inferior, corpus geniculatum mediale and Heschl’s gyrus. The results were compared with those of the control group.

Results: The ADC values of lateral lemniscus, colliculus inferior and corpus geniculatum mediale were significantly higher in NF1 compared to those of the control group. On the other hand, decreased FA values were observed in lateral lemniscus and colliculus inferior in patients with NF1.

Conclusion: The increase in ADC and reduction in FA in the auditory pathways of patients with NF1 may suggest microstructural alterations, such as a decrease in the number of axons, edema or inflammation in the auditory tracts. To read out more, please visit: http://www.eurekaselect.com/161550/article

Most Accessed Articles | Identification of New Inhibitors of Mutant Isocitrate Dehydrogenase 2 through Molecular Similarity-based Virtual Screening

Journal Name: Letters in Drug Design & Discovery

Author(s): Lijun Yang, Stefan Pusch, Victoria Jennings, Tianfang Ma, Qihua Zhu, Yungen Xu, Andreas von Deimling*, Xiaoming Zha*.

 

 

 

 

Graphical Abstract:

 

Abstract:

Background: Isocitrate dehydrogenase 2 (IDH2) is an enzyme catalyzing the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) in the tricarboxylic acid (TCA). Evidences suggest that the specific mutations in IDH2 are critical to the growth and reproduction of severe tumors especially leukemia and glioblastoma. It is found that the inhibitors of mutant IDH2 are promising anti-tumor therapeutics.

Methods: A virtual screening strategy combining molecular similarity search and molecular docking was performed in the binding site of AGI-6780. YL-16, YL-17 and YL-18 were identified as novel mutant IDH2 inhibitors for the reduction of (D)-2-hydroxyglutarate in cellular evaluation. In addition, all the three compounds showed inhibition against IDH2-R172K mutated HEK-293T cells, while weak inhibition against wide-type IDH2 (WT-IDH2) HEK-293T cells.

Results: Significantly, YL-17 showed 84.55% inhibitory activity against IDH2-R172K at 1 µM and weak cytotoxicity to wide-type IDH2 at 50 µM.

Conclusion: YL-17 was highlighted as a new mutant IDH2 inhibitor that could be further developed for therapeutic applications. To read out more, please visit: http://www.eurekaselect.com/164444/article

Most Accessed Articles | Development of an HPLC-UV Method for Quantification of Stattic

Journal Name: Current Pharmaceutical Analysis

Author(s): Soheil Sedaghat, Ommoleila Molavi, Akram Faridi, Ali Shayanfar*, Mohammad Reza Rashidi.

Graphical Abstract:

 

 

Abstract:

Background: Signal transducer and activator of transcription 3 (STAT3), an oncogenic protein found constitutively active in many types of human malignancies, is considered to be a promising target for cancer therapy.

Objective: In this study for the first time, a simple and accurate method has been developed for the determination of a STAT3 dimerization inhibitor called stattic in aqueous and plasma samples.

Methods: A reverse-phase high-performance liquid chromatography (RP-HPLC) composed of C18 column as stationary phase, and the mixture of acetonitrile (60%) and water (40%) as mobile phase with a UV detection at 215 nm were applied for quantification of stattic. The developed method was validated by Food and Drug Administration (FDA) guideline.

Results: The method provided a linear range between 1-40 and 2.5-40 µg mL-1 for aqueous and plasma samples, respectively, with a correlation coefficient of 0.999. The accuracy (as recovery) of the developed method was found to be between 95-105% for aqueous medium and 85-115% for plasma samples. The precision (as relative standard deviation) for aqueous and plasma samples was less than 6% and 15%, respectively. The sensitivity of the developed method based on FDA guideline was 1 µg mL-1 for aqueous and 2.5 µg mL-1 for plasma samples.

Conclusion: These results show that the established method is a fast and accurate quantification for stattic in aqueous and plasma samples. To read out more, please visit: http://www.eurekaselect.com/162366/article

Most Accessed Articles | QSAR Analysis of Multimodal Antidepressants Vortioxetine Analogs Using Physicochemical Descriptors and MLR Modeling

Journal Name: Current Computer-Aided Drug Design

Author(s): David M. Rajathei*, Subbiah Parthasarathy, Samuel Selvaraj.

 

 

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Abstract:

Background: Vortioxetine is a multimodal antidepressant drug with combined effects on SERT as an inhibitor, 5-HT1A as agonist and 5-HT3A as an antagonist. Series of vortioxetine analogs have been reported as multi antidepressant compounds and they block serotonin transport into the neuronal cells, activate the postsynaptic 5-HT1A receptors and eliminate the low activity of 5-HT3A receptors.

Objective: To explore the important properties of vortioxetine analogs involved in antidepressant activity by developing 2D QSAR models.

Methods: Selections of significant descriptors were performed by Least Absolute Shrinkage and Selection Operator (LASSO) method and, the Multiple Linear Regression (MLR) method and All Subsets and GA algorithm included in QSARINS software were used for generating QSAR models. Further, the virtual screening was performed based on bioactivity and structure similarity using the PubChem database.

Results: The four descriptor model of complementary information content (CIC2), solubility (bcutp3), mass (bcutm8) and partial charge in van der Waals surface area (PEOEVSA7) of the molecules is obtained for SERT inhibition with the significant statistics of R2= 0.69, RMSEtr= 0.44, R2 ext= 0.62 and CCCext= 0.78. For 5-HT1A agonist, the two descriptor model of molecular shape (Kappm3) and van der Waals volume of the atoms (bcutv11) with R2= 0.78, RMSEtr= 0.33, R2 ext = 0.83, and CCCext= 0.87 is established. The three descriptor model of information content (IC3), solubility (bcutp9) and electronegativity (GATSe5) of the molecules with R2= 0.61, RMSEtr= 0.34, R2 ext= 0.69 and CCCext= 0.72 is obtained for 5-HT3A antagonist. The antidepressant activities of 16 virtual screened compounds were predicted using the developed models.

Conclusion: The developed QSAR models may be useful to predict antidepressant activity for the newly synthesized vortioxetine analogs. To read out more, please visit: http://www.eurekaselect.com/166166/article

Most Accessed Articles | Molecular Diagnosis of Fibro-osseous Lesions of the Oral and Maxillofacial Region: A Tale from Africa

Journal Name: Current Dentistry

Author(s): Olujide O. Soyele, Adeyinka H. Adedapo, Henry A. Adeola*.

 

 

Fibro-osseous lesions (FOLs) are a poorly defined but pathologically diverse group of lesions affecting the craniofacial bones and jaw. They are mostly characterized by the replacement of bone by a benign connective tissue matrix, which may contain foci of mineralization in the form of woven bone or cementum-like round acellular intensely basophilic structures. These lesions, although diverse, often present similar clinico-pathological and radiographic features. This often leads to difficulty in diagnosis and management. Definitive diagnosis is often reached only by incisional or excisional biopsy in resource-limited settings. Epidemiologically, the incidence and prevalence of different FOLs have been variable depending on the region. Reports from Africa indicated that FOLs make up to 10% of all oral biopsies, while others have given lower figures. A good understanding of the pathogenetic mechanism for FOLs is important, and state of the art molecular approaches are bound to improve the diagnosis and delineation of various entities that fall under the FOL category. Not least, the classification and nomenclature of these lesions by the World Health Organization (WHO) have changed significantly over the years. Hence, we have presented in this review a robust discussion on the pathobiology, emerging molecular markers, diagnostic challenges, future perspectives and recent changes to the classification/nomenclature of FOLs by WHO. In addition, we also discussed the diagnostic bottlenecks encountered during diagnosis of FOL in Africa. To read out more, please visit: http://www.eurekaselect.com/163030/article

Most Accessed Articles | Antibacterial Profile of Copaifera multijuga Oleoresin and Hydroalcoholic Extract of Leaves Against Oral Pathogens

 

Journal Name: Current Dentistry

Author(s): Iane Pereira Pimenta, Fariza Abrão, Jonas Joaquim Mangabeira da Silva, Larissa Costa Oliveira, Hervé Louis Ghislain Rogez, Sérgio Ricardo Ambrósio, Rodrigo Cássio Sola Veneziani, Jairo Kenupp Bastos, Carlos Henrique Gomes Martins*.

 

 

Background: Copaifera multijuga are widely used as medicinal plants in Brazil. Of the various ethnopharmacological indications of copaiba oleoresins, the antimicrobial activity had been highlighted.

Objective: This study aimed to evaluate the oleoresin and the hydroalcoholic extract of leaves from Copaifera multijuga against oral pathogens in the sessile and in the planktonic modes.

Methods: Standard strains from the American Type Culture Collection and clinical isolates which cause both cariogenic and endodontic infections were used. Was evaluated in terms of its Minimum Inhibitory Concentration (MIC) values by the broth microdilution method in 96-well microplates, Minimum Bactericidal Concentration (MBC) and biofilm eradication assay.

Results: The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) assays showed that the oleoresin was effective against some the bacterial strains. Assessment of the antibiofilm activity of hydroalcoholic extract of leaves from C. multijuga against the evaluated microaerophilic bacteria in the sessile mode gave IC50 values of 318.0 and 695.6 µg/mL against S. mitis (ATCC 49456) and A. actinomycetemcomintans (ATCC 43717), respectively. As for the assayed anaerobic bacteria, the hydroalcoholic extract of leaves gave IC50 of 4554.0, 2218.0, and 600.1 µg/mL against F. nucleatum (Clinical isolate), P. gingivalis (ATCC 33277), and P. micros (Clinical isolate), respectively, whereas the oleoresin afforded IC50 of 357.1 µg/mL against P. gingivalis (ATCC 33277).

Conclusion: The oleoresin and hydroalcoholic extract of leaves displayed satisfactory activity against the main oral pathogens in both sessile and planktonic modes. The oleoresin and hydroalcoholic extracts of leaves from C. multijuga are potential candidates for the development of new products for dental and oral care. To read out more, please visit: http://www.eurekaselect.com/163330/article

Most Accessed Articles | Dysfunctional Mechanism of Liver Cancer Mediated by Transcription Factor and Non-coding RNA

Journal Name: Current Bioinformatics

Author(s): Wei Zeng, Fang Wang, Yu Ma, Xianchun Liang, Ping Chen*.

 

 

 

Background: There have been numerous experiments and studies on liver cancer by biomedical scientists, while no comprehensive and systematic exploration has yet been conducted. Therefore, this study aimed to systematically dissect the transcriptional and non-coding RNAmediated mechanisms of liver cancer dysfunction.

Method: At first, we collected 974 liver cancer associated genes from the Online Mendelian Inheritance in Man (OMIM). Afterwards, their interactors were recruited from STRING database so as to identify 18 co-expression modules in liver cancer patient expression profile. Crosstalk analysis showed the interactive relationship between these modules. In addition, core drivers for modules were identified, including 111 transcription factors (STAT3, JUN and NFKB1, etc.) and 1492 ncRNAs (FENDRR and miR-340-5p, etc.) Read out full article here: http://www.eurekaselect.com/167479

Most Accessed Articles | Synthesis and Biological Evaluation of PF-543 Derivative

 

Journal Name: Letters in Organic Chemistry

Author(s): Seon Woong Kim, Taeho Lee, Joo-Youn Lee, Sanghee Kim, Hee-Sook Jun, Eun-Young Park*, Dong Jae Baek*.

 

PF-543 has been known as a substance that strongly inhibits SK1. However, it also exhibits antineoplastic activity that is lower than other inhibitors of SK1. In this study, we compared PF-543 and synthesized a newly designed derivative of PF-543 (compound 2) in which two aromatic structures were connected in para-form. The synthesized derivative showed inhibitory effect on SK1, similar to that of PF-543. However, it was more cytotoxic to HT29, AGS, and PC3 cells than PF-543. We also carried out a docking study for SK1 and demonstrated that the synthesized derivative showed interaction with SK1 similar to PF-543. Results obtained from this study suggest that the structure of compound 2 may be well substituted for the structure of PF-543 in terms of biological activity, providing us important structural information for the design of new derivatives of PF-543. Read out full article here: http://www.eurekaselect.com/166082

 

Most Accessed Articles | A Review of Denoising Medical Images Using Machine Learning Approaches

Author(s): Prabhpreet Kaur*, Gurvinder Singh, Parminder Kaur.

Journal Name: Current Medical Imaging

 

This paper attempts to identify suitable Machine Learning (ML) approach for image denoising of radiology based medical application. The Identification of ML approach is based on (i) Review of ML approach for denoising (ii) Review of suitable Medical Denoising approach.

The review focuses on six application of radiology: Medical Ultrasound (US) for fetus development, US Computer Aided Diagnosis (CAD) and detection for breast, skin lesions, brain tumor MRI diagnosis, X-Ray for chest analysis, Breast cancer using MRI imaging. This survey identifies the ML approach with better accuracy for medical diagnosis by radiologists. The image denoising approaches further includes basic filtering techniques, wavelet medical denoising, curvelet and optimization techniques. In most of the applications, the machine learning performance is better than the conventional image denoising techniques. For fast and computational results the radiologists are using the machine learning methods on MRI, US, X-Ray and Skin lesion images. The characteristics and contributions of different ML approaches are considered in this paper. Read out full article here: http://www.eurekaselect.com/152027